This invention generally relates to coated medical devices and to procedures for coating and administering same. More particularly, a thiol group containing agent is loaded onto a medical device for in vivo interaction with a nitric oxide donor. In the illustrated preferred embodiment, protected sulfur containing compounds are covalently attached onto medical device surfaces of polymer-coated metals, polymers and the like. These thus immobilized compounds, when deprotected, present sulfhydryl groups which are useful for enhancing local release of nitric oxide in vivo, or at the site of an implanted medical device and the like, when a nitric oxide donor such as a vasodilator is administered. Such nitric oxide release is of value, for example, in preventing platelet aggregation and smooth muscle cell proliferation. Possible thrombosis and/or restenosis which might be associated with the device implant is thereby minimized or even eliminated.
The liberation of nitric oxide from vasodilators, particularly nitric oxide donors, is generally believed to be potentiated by thiol donors. To the extent that thiol group containing agents are efficacious with respect to nitric oxide release, such can enhance the effectiveness of a nitric oxide containing agent or compound. It is accordingly believed that the effectiveness of vasodilators can be enhanced by their interaction with compounds which contain thiol groups. Observations made in this regard are discussed in Anderson, et al., "Nitric Oxide and Nitrovasodilators: Similarities, Differences and Potential Interactions", Journal American College of Cardiology, Vol. 24, pages 555-566, August, 1994, and in Welch, et al., "Nitric Oxide as a Vascular Modulator", Circulation, Vol. 87, pages 1461-1467, 1993, both incorporated hereinto by reference.
Concerns with respect to clinical and interventional procedures, including those involving vascular implants for example, include stenosis development or restenosis over time. In this regard, endoprostheses such as stents, catheters or any other device which is contacted by blood during a clinical or interventional procedure in the vascular system, run the risk of stenosis development. For example, a stent which had been implanted in order to address a stenosis situation would be much more desirable and efficacious if the stent itself discouraged stenosis at the implantation site.
Accordingly, approaches are needed which will directly address stenosis and restenosis concerns with respect to vascular implants. For example, it can be important to prevent smooth muscle cell proliferation, which has been associated with restenosis. Also to be prevented is platelet aggregation and its attendant thrombosis development.
Biocompatibility enhancement of vascular implants such as stents and the like can include coating treatment approaches. An example in this regard is Narayanan et al U.S. Pat. No. 5,336,518, incorporated by reference hereinto. With this technology, bioactive agents are secured to a metal surface of a medical device by an approach which includes treating a metal surface having a polymeric coating with water vapor plasma in order to facilitate attachment of the biologically active agent to the polymer coating. Various biologically active agents are discussed, including numerous agents such as the heparins and vasodilators.